The long term objective of this research proposal is to develop a laser induced fluorescence based clinical system for real time detection of oral precancerous lesions. The proposed program will combine clinical and experimental studies to characterize fluorescence properties of healthy and diseased oral mucosa. First, in vivo multi-excitation fluorescence and reflectance spectra will be acquired to select optimal excitation wavelength(s) for accurate diagnosis. Clinical studies will then be performed using the appropriate excitation wavelength(s) to study spectral features of a variety of oral lesions. Microspectroscopy and microscopic imaging techniques will be utilized to understand the molecular and morphological basis or oral mucosa fluorescence. Statistically-based empirical and model-based diagnostic algorithms will be developed. Progression studies will be performed in an animal model to understand the dynamic changes in fluorescence features in increasing degrees of dysplasia. The knowledge gained from this study may lead to the development of a simple, inexpensive and non-invasive diagnostic tool for oral cancer screening in a dentist's office and guiding biopsy and follow up of suspicious oral lesions by otolaryngologists and oral surgeons.